PB1935: MANAGEMENT OF NON-SEVERE APLASTIC ANEMIA: LABORATORY WORKUP AND TREATMENT PATTERNS.
Authors: G. Cassanello, J. A. Giannotta, L. Cro, M. Barbieri, W. Barcellini, B. Fattizzo
Journal: HemaSphere (2022)

Background: Non severe aplastic anemia (NSAA) is a rare and heterogeneous disease characterized by different cytopenias and variable severity and possible evolution into myeloid neoplasms. Data on clinical workup and therapeutic strategies adopted are largely lacking due to the rarity of the disease and the limited number of dedicated clinical trials. Aims: To outline disease features, management and adverse events in 25 NSAA patients followed at a single tertiary hematologic center Methods: We evaluated all patients diagnosed with NSAA according to Camitta criteria (hypocellular bone marrow with peripheral blood values not meeting criteria for severe AA) at a single tertiary hematologic center in the last 20 years. We collected baseline hematologic features, bone marrow biopsies, flow-cytometry (FCM) of marrow aspirates and mutational status by next generation sequencing (NGS) for 69 genes involved in myeloid neoplasms. Different management strategies were registered retrospectively and categorized in 1) steroids +/- cyclosporin (CyA), 2) eltrombopag + CyA and 3) watch & wait. Responses were evaluated according to 2009 Marsh criteria Results: We included 25 patients, mainly females (64%) and with a median age of 48 years (17-91) (Table 1). The most frequent cytopenia was thrombocytopenia (N=22) and 1/3 of cases were transfusion dependent. Bone marrow samples showed a median cellularity of 15% (range 5-30), with dyserythropoiesis in 44%, dysmyelopoiesis in 16%, and reticulin fibrosis (MF-1) in 16% of patients. Bone marrow microenvironment by FCM appeared enriched for lymphocytes (22% of the total cellularity, range 7-58), particularly T lymphocytes (median 72%, range 58-97). A minor infiltrate of monocytes (median 3.3%, range 0.6-5) and mast-cells (median 0.5 %, range 0.02-2) was also detected. NGS for mutations in myeloid genes showed that 7/9 had negative results, whilst 1 patient harbored NF1 and U2AF1 mutations (VAF 4.7% and 4.9%, respectively), and one harbored a germline SBDS mutation (VAF 48%). The latter had a concurrent familiar history of myeloid neoplasm and the mutation was confirmed on cutaneous biopsy. During a median follow up of 21 months (range 1-187), 16/25 patients received treatment. These patients showed more profound cytopenias and a higher frequency of small PNH clones (p=0.02) as compared to untreated cases (Table 1). Eight patients were treated with CyA and the other 8 with eltrombopag+CyA. The overall response rate (CR+PR) in the former group at 3, 6 and 12 months were 66%, 100% and 100%, respectively. In the second one, the corresponding response rates were 57%, 49% and 100%, with no significant differences between treatment groups. Seven patients (43%) experienced one or more adverse events (AEs), mostly grade 1 or 2 according to CTCAE. Grade 3/4 toxicities were all registered in the eltrombopag+CyA and consisted in retinal thrombosis, gastroenteritis, diarrhea and acute hepatitis. The sudden rise of transaminases and bilirubin levels was registered in 3 patients and led to treatment discontinuation. Single agent eltrombopag was subsequently readministered due to loss of platelet response in 2/3 patients, with no further toxicity to date. Image:Summary/Conclusion: In conclusion we observed that NSAA required treatment in about 2/3 of cases characterized by more severe cytopenias. Treatment with CyA+/- eltrombopag led to a significant clinical improvement. Occurrence of G3 liver toxicity in patients receiving combination therapy deserves attention and further studies. FCM showed a prominent T-cell infiltrate reflecting the prominent cell mediated autoimmunity of the disease.